SLCO1B3 polymorphisms and clinical outcomes in kidney transplant recipients receiving mycophenolate

2021 ◽  
Author(s):  
Lauren Schumacher ◽  
Fang Fang ◽  
Kelley M Kidwell ◽  
Faisal Shakeel ◽  
Daniel L Hertz ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
Patient Survival ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Primary Analysis ◽  
Adult Kidney ◽  
Increased Risk

Aim: Determine the influence of SLCO1B3 polymorphisms on outcomes in kidney transplant recipients. Materials & methods: We retrospectively evaluated 181 adult kidney transplant recipients receiving mycophenolate. Outcomes included treated biopsy-proven acute rejection (tBPAR), de novo donor specific antibody (dnDSA) formation, graft survival, patient survival and mycophenolate-related adverse effects among SLCO1B3 genotypes. Results: The presence of SLCO1B3 variants was not associated with increased risk of tBPAR (HR: 1.45, 95% CI: 0.76–2.74), dnDSA (HR: 0.46, 95% CI: 0.16–1.36) or composite of tBPAR or dnDSA (HR: 1.14, 95% CI: 0.64–2.03). Graft and patient survival were reduced among variant carriers; however, inconsistent findings with the primary analysis suggest these associations were not due to genotype. Adverse effects were similar between groups. Conclusion: Presence of SLCO1B3 polymorphisms were not predictive of rejection or dnDSA in kidney transplant recipients.

scholarly journals Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2893 ◽  
Author(s):  
Rossana Rosa ◽  
Jose F. Suarez ◽  
Marco A. Lorio ◽  
Michele I. Morris ◽  
Lilian M. Abbo ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Acute Rejection ◽  
Clinical Outcomes ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Patient Survival ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Serious Infections ◽  
The Impact

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.

scholarly journals Incidence and Impacts of Inflammatory Bowel Diseases among Kidney Transplant Recipients: A Meta-Analysis

2020 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Panupong Hansrivijit ◽  
Max M. Puthenpura ◽  
Charat Thongprayoon ◽  
Himmat S. Brar ◽  
Tarun Bathini ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
De Novo ◽  
Meta Analysis ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Adult Kidney ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background: The incidence of inflammatory bowel diseases (IBD) and its significance in kidney transplant recipients is not well established. We conducted this systematic review and meta-analysis to assess the incidence of and complications from IBD in adult kidney transplant recipients. Methods: Eligible articles were searched through Ovid MEDLINE, EMBASE, and the Cochrane Library from inception through April 2020. The inclusion criteria were adult kidney transplant patients with reported IBD. Effect estimates from the individual studies were extracted and combined using the fixed-effects model when I2 ≤ 50% and random-effects model when I2 > 50%. Results: of 641 citations, a total of seven studies (n = 212) were included in the systematic review. The mean age was 46.2 +/− 6.9 years and up to 51.1% were male. The mean duration of follow-up was 57.8 +/− 16.8 months. The pooled incidence of recurrent IBD was 27.6% (95% CI, 17.7–40.5%; I2 0%) while the pooled incidence of de novo IBD was 18.8% (95% CI, 10.7–31.0%; I2 61.3%). The pooled incidence of post-transplant IBD was similar across subgroup analyses. Meta-regression analyses showed no association between the incidence of IBD and age, male sex, and follow-up duration. For post-transplant complications, the pooled incidence of post-transplant infection was 4.7% (95% CI, 0.5–33.3%; I2 73.7%). The pooled incidence of graft rejection and re-transplantation in IBD patients was 31.4% (95% CI, 14.1–56.1%; I2 76.9%) and 30.4% (95% CI, 22.6–39.5%; I2 0%). Conclusion: Recurrent and de novo IBD is common among kidney transplant recipients and may result in adverse outcomes.

scholarly journals Cardiovascular calcifications in kidney transplant recipients

2021 ◽  
Author(s):  
Manuel Alfredo Podestà ◽  
David Cucchiari ◽  
Paola Ciceri ◽  
Piergiorgio Messa ◽  
José-Vicente Torregrosa ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Transplant ◽  
De Novo ◽  
Immunosuppressive Drugs ◽  
Current Evidence ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Increased Risk ◽  
Cardiovascular Calcifications

AbstractVascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.

scholarly journals Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation

2018 ◽  
Vol 29 (7) ◽  
pp. 1979-1991 ◽  
Author(s):  
Julio Pascual ◽  
Stefan P. Berger ◽  
Oliver Witzke ◽  
Helio Tedesco ◽  
Shamkant Mulgaonkar ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Confidence Interval ◽  
Kidney Transplant ◽  
Calcineurin Inhibitor ◽  
De Novo ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
End Point

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR<50 ml/min per 1.73 m2 at post-transplant month 12 using a 10% noninferiority margin.Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, −1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, −1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was noninferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

scholarly journals P1779NOVEL ONCE-DAILY EXTENDED-RELEASE TACROLIMUS VERSUS TWICE -DAILY TACROLIMUS IN DE NOVO KIDNEY TRANSPLANT RECIPIENTS DURING THE EARLY POSTTRANSPLANT PERIOD

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Volkan Polatkan ◽  
Ebru Ozdemir ◽  
Turker Erturk ◽  
Emel Tatli ◽  
Ibrahim Berber ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Serum Creatinine ◽  
Kidney Transplant ◽  
Whole Blood ◽  
De Novo ◽  
Prolonged Release ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Once Daily ◽  
Group Ii

Abstract Background and Aims Both under and over-dosing of tacrolimus may compromise clinical outcomes by exposing patients to either the risks of graft rejection or adverse events (AEs) associated with immunosuppressive therapy. This study is designed to compare the clinical follow-up of our kidney transplant recipients receiving once-daily, prolonged-release (PR-T; Advagraf) and twice-daily, immediate-release (IR-T; Prograf) tacrolimus in the early posttransplant period. Method This randomized study included 78 de novo, adult kidney transplant recipients to PR-T 0.15 mg/kg/day (Group I=39) and IR-T 0.15 mg/kg/day (Group II=39) for seven days in the posttransplant period. Demographic features and clinical parameters regarding levels of whole blood tacrolimus and serum creatinine were compared between the two groups. Presence of acute rejection and AEs were investigated. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations in all patients. SPSS 15 for Windows was used for statistical analysis. Results None of the patients suffered from acute rejection and there were no AEs in the early posttransplant period. However, Group II patients were found to have higher whole blood tacrolimus levels on the posttransplant 1st, 4th and 7th days (p=0.02, p=0.009 and p=0.013 respectively). Also serum creatinine levels were significantly increased in Group II patients on the posttransplant 7th day (p=0.02). Conclusion Prolonged release tacrolimus seems promising in preventing acute transplant rejection with adequate blood levels, as well as making it possible to avoid the interindividual variation in absorption and early calcineurin inhibitor toxicity.

Donor-Specific Anti-Human Leukocyte Antigens Antibodies, Acute Rejection, Renal Function, and Histology in Kidney Transplant Recipients Receiving Tacrolimus and Everolimus

2017 ◽  
Vol 45 (6) ◽  
pp. 497-508 ◽  
Author(s):  
Alexandra Ferreira ◽  
Claudia Felipe ◽  
Marina Cristelli ◽  
Laila Viana ◽  
Geovana Basso ◽  
...  
Keyword(s):  
Renal Function ◽  
Acute Rejection ◽  
Kidney Transplant ◽  
De Novo ◽  
Human Leukocyte ◽  
Comparable Efficacy ◽  
Human Leukocyte Antigens ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Leukocyte Antigens

Background: This analysis compared efficacy, renal function, and histology in kidney transplant recipients receiving tacrolimus (TAC) combined with everolimus (EVR) or mycophenolate (MPS). Methods: This was a retrospective analysis from a randomized trial in kidney transplant recipients who received a single 3 mg/kg dose of rabbit antithymocyte globulin (r-ATG), TAC, EVR, and prednisone (PRED; r-ATG/EVR, n = 85), basiliximab (BAS), TAC, EVR, and PRED (BAS/EVR, n = 102) or BAS, TAC, MPS, and PRED (BAS/MPS, n = 101). We evaluated the incidence of de novo donor-specific anti-human leukocyte antigens antibodies (DSA) and histology on protocol biopsies at 12 months, and the incidence of acute rejection, estimated glomerular filtration rate (eGFR) and proteinuria at 36 months. Results: At 12 months, there were no differences in de novo DSA (6.4 vs. 3.4 vs. 5.5%) or in subclinical inflammation (2.0 vs. 4.8 vs. 10.2%), interstitial fibrosis/tubular atrophy (57.1 vs. 58.5 vs. 53.8%) and C4d deposition (2.0 vs. 7.3 vs. 2.6%). At 36 months, there were no differences in the incidence of treatment failure (19.0 vs. 27.7 vs. 27.7%, p = 0.186), first biopsy-proven acute rejection (9.5 vs. 21.8 vs. 16.8%, p = 0.073), and urine protein/creatinine ratios (0.53 ± 1.05 vs. 0.62 ± 0.75 vs. 0.71 ± 1.24). eGFR was lower in the BAS/EVR compared to that in the BAS/MPS group (53.4 ± 20.9 vs. 50.8 ± 19.5 vs. 60.7 ± 21.2 mL/min/1.73 m2, p = 0.017) but comparable using a sensitive analysis (49.5 ± 23 vs. 47.5 ± 22.6 vs. 53.6 ± 27.8 mL/min/1.73 m2, p = 0.207). Conclusion: In this cohort, the use of EVR and reduced TAC concentrations were associated with comparable efficacy, renal function, and histological parameters compared to the standard-of-care immunosuppressive regimen.

scholarly journals Side Effect Driven Conversion to Belatacept for Kidney Transplant Recipients in a Clinical Setting

2020 ◽  
Vol 5 (1) ◽  
Keyword(s):  
Adverse Effects ◽  
Kidney Transplant ◽  
Patient Survival ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Transplant Patients ◽  
Immunosuppressive Medication ◽  
Maintenance Immunosuppression ◽  
Kidney Transplant Patients ◽  
One Year

Maintenance immunosuppression after kidney transplantation is critical to graft and patient survival. However, the optimal immunosuppressive medication may differ for patients based on adverse effects. Here we report one-year outcomes of 73 kidney transplant patients converted from tacrolimus to belatacept because of adverse effects at least 90 days after transplant.

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